ph i study of lithium during whole brain radiotherapy for patients with brain metastases

Conditions: Brain and Central Nervous System Tumors; Cognitive/Functional Effects; Neurotoxicity; Solid Tumor

Summary: rationale: radiation therapy uses high-energy x-rays to kill tumor cells. drugs, such as lithium, may protect normal cells from the side effects of radiation therapy. giving lithium together with radiation therapy may allow a higher dose of radiation therapy to be given so that more tumor cells are killed. purpose: this phase i trial is studying the side effects and best dose of lithium when given together with whole-brain radiation therapy in treating patients with brain metastases from primary cancer outside the brain.

objectives: * determine the feasibility of concurrent lithium carbonate and whole-brain radiotherapy, as measured by safety and compliance, in patients with primary extracranial malignancy and brain metastases. outline: this is an open-label, dose-escalation study of lithium carbonate. patients receive oral lithium carbonate twice daily on days 1-7 and 2-4 times daily on days 8-21. patients undergo whole-brain radiotherapy once daily on days 8-12 and 15-19. cohorts of 3-6 patients receive escalating doses of lithium carbonate until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. quality of life and mental status are assessed at baseline, on days 1, 8, and 15, at 1-month post-treatment, and then periodically thereafter. after completion of study treatment, patients are followed at 1 month and then periodically thereafter. projected accrual: a total of 24 patients will be accrued for this study.

Eligibility criteria:
inclusion criteria: * histopathologically confirmed extracranial primary malignancy * multiple (i.e., \> 3) brain metastases or \ 4.0 cm in diameter * not eligible for radiosurgery * no requirement for immediate whole-brain radiotherapy * no metastases to the midbrain or brainstem exclusion criteria: * zubrod performance status 0-2 * life expectancy ≥ 8 weeks * platelet count \> 100,000/mm\^3 * anc \> 1,500/mm\^3 * hemoglobin ≥ 10 g/dl * bun \< 25 mg/dl * creatinine \< 1.5 mg/dl * bilirubin \< 1.5 mg/dl * alt ≤ 2 times normal * sodium \> 136 mg/dl * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * neurologically stable * no seizure disorders or seizures due to brain metastases * no medical illnesses or psychiatric conditions that would preclude completion of study treatment * no sensory neuropathy ≥ grade 2 * no bipolar disorder * no thyroid disease * no qtc interval prolongation prior concurrent therapy: * more than 2 weeks since prior and no concurrent chemotherapy * at least 2 weeks since prior and no concurrent nsaids, angiotensin-converting enzyme inhibitors (e.g., enalapril or captopril), calcium channel blockers, diuretics, selective cyclooxygenase-2 inhibitors, acetazolamide, urea, xanthine, or alkalinizing agents (e.g., sodium bicarbonate) * no prior radiotherapy to the head and neck area * no prior radiosurgery * no concurrent radiotherapy to other sites * no concurrent anticonvulsants due to brain metastases * no concurrent psychoactive drugs * no concurrent thyroid medications * no concurrent amifostine

Keywords: radiation toxicity neurotoxicity cognitive/functional effects unspecified adult solid tumor, protocol specific adult tumors metastatic to brain